Does intensive insulin therapy really reduce mortality in critically ill surgical patients? A re-analysis of meta-analytic data

Two recent systematic reviews evaluating intensive insulin therapy (IIT) in critically-ill patients grouped randomized controlled trials (RCTs) by type of intensive care unit (ICU). The more recent review found that IIT reduced mortality in patients admitted to a surgical ICU, but not in those admitted to medical or mixed medical-surgical ICUs, or in all patients combined. Our objective was to determine whether IIT saves lives in critically-ill surgical patients regardless of type of ICU. Pooling mortality data from surgical and medical subgroups in mixed-ICU RCTs (16 trials) with RCTs conducted exclusively in surgical ICUs (5 trials) and medical ICUs (5 trials), respectively, showed no effect of IIT in the subgroup of surgical patients (RR 0.85 [95% CI 0.69-1.04, P=0.11]; I2=51% [95% CI 1-75%]) or medical patients (RR 1.02 [95% CI 0.95-1.09, P=0.61]; I2=0% [95% CI 0-41%]). There was no differential effect between subgroups (interaction P=0.10). There was statistical heterogeneity in the surgical subgroup, with some trials demonstrating significant benefit and others demonstrating significant harm, but no surgical subgroup consistently benefited from IIT. Such a re-analysis suggests that IIT does not reduce mortality in critically ill surgical or medical patients. Further insights may come from individual patient data meta-analyses or from future large multicentre RCTs in more narrowly defined subgroups of surgical patients.